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The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions.

Tight junctions form an intercellular barrier between epithelial cells, serve to separate tissue compartments, and maintain cellular polarity. Paracellular sealing properties vary among cell types and are regulated by undefined mechanisms. Sequence of the full-length cDNA for human ZO-1, the first identified tight junction component, predicts a protein of 1736 aa. The N-terminal 793 aa are homologous to the product of the lethal(1)discs-large-1 (dlg) tumor suppressor gene of Drosophila, located in septate junctions, and to a 95-kDa protein located in the postsynaptic densities of rat brain, PSD-95. All three proteins contain both a src homology region 3 (SH3 domain), previously identified in membrane proteins involved in signal transduction, and a region homologous to guanylate kinase. ZO-1 contains an additional 943-aa C-terminal domain that is proline-rich (14.1%) and contains an alternatively spliced domain, whose expression was previously shown to correlate with variable properties of tight junctions. dlg mutations result in loss of apical-basolateral epithelial cell polarity and in neoplastic growth. These results suggest a protein family specialized for signal transduction on the cytoplasmic surface of intercellular junctions. These results also provide biochemical evidence for similarity between invertebrate septate and vertebrate tight junctions. The C-terminal domain of ZO-1, and its alternatively spliced region, appears to confer variable properties unique to tight junctions.

Pubmed ID: 8395056


  • Willott E
  • Balda MS
  • Fanning AS
  • Jameson B
  • Van Itallie C
  • Anderson JM


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 15, 1993

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK07356
  • Agency: NIDDK NIH HHS, Id: DK34989
  • Agency: NIDDK NIH HHS, Id: DK45134

Mesh Terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain
  • Cell Membrane
  • Cloning, Molecular
  • DNA
  • Drosophila
  • Drosophila Proteins
  • Epithelium
  • Gene Library
  • Genes, Lethal
  • Genes, Tumor Suppressor
  • Guanylate Kinase
  • Humans
  • Insect Hormones
  • Intercellular Junctions
  • Membrane Proteins
  • Molecular Sequence Data
  • Nucleoside-Phosphate Kinase
  • Phosphoproteins
  • Proline
  • Rats
  • Restriction Mapping
  • Sequence Homology, Amino Acid
  • Synapses
  • Tumor Suppressor Proteins
  • Zonula Occludens-1 Protein